Diastereodivergent Access to cis , cis - and cis , trans -Angular Triquinanes: Total Synthesis of (±)-Arnicenone
En palabras de los autores
Abstract Angular triquinanes constitute an important class of polycyclic natural products characterized by compact, angularly fused ring systems and multiple contiguous stereocenters. Herein, we report a diastereodivergent strategy for stereocontrolled access to both cis,trans- and cis,cis-angular triquinanes from common allene precursors. The cis,trans-fused triquinanes were constructed through a Lewis acid-promoted intramolecular [3+2] Danheiser annulation, whereas the complementary cis,cis frameworks were accessed via photochemical [2+2] cycloaddition followed by oxidative ring expansion. Notably, substitution at the R1 position of the allene precursor reversed the diastereoselectivity of the [3+2] annulation, providing direct access to a cis,cis-angular triquinane. DFT calculations indicate that the initial spirocyclization governs both the reactivity and stereochemical outcome of the [3+2] pathway, with substrate-dependent steric interactions accounting for the observed diastereodivergence. The synthetic utility of this strategy was demonstrated through the total synthesis of (±)-arnicenone via the [2+2] cycloaddition/oxidative ring-expansion pathway, while an alternative synthesis from the cis,cis-[3+2] Danheiser annulation product further highlights the complementary nature of the two approaches. Together, these results establish a unified platform for stereodivergent access to angular triquinanes and their application to complex natural product synthesis.
Apareció: jueves, 24 de septiembre. Journal of the American Chemical Society. Revista con revisión por pares.
DOI: 10.1021/jacs.6c09019